The kidney functions as an essential excretory device adept in the intricate regulation and maintenance of the physicochemical milieu of the human body. By finely tuning the balance of water, electrolytes, and other vital substances, this organ elegantly stabilizes the internal environment of the body and could rightfully be considered a linchpin of homeostasis (1). Severe or persistent kidney damage often leads to tubular degeneration, inflammation, renal fibrosis, and ultimately chronic kidney disease (CKD) or end-stage renal disease (2). It is well known that both acute kidney injury (AKI) and CKD have become important clinical problems and global public health issues, affecting more than 750 million people worldwide (3). It is estimated that 17 million hospitalized patients experience AKI each year, with a significant increase in mortality, length of stay and the development of other complications (4). The population prevalence of chronic kidney disease exceeds 10% and in high-risk subpopulations exceeds 50% (5). Kidney diseases pose a serious burden on global health as well as on healthcare systems.

A growing number of studies suggest that RNA modifications play an integral role in the development of renal diseases. RNA modifications are chemical modifications that occur at different atoms of bases and are of numerous types; more than 170 chemical modifications have been identified on RNA to date, and more than half are methylation modifications. The distribution sites involve a variety of RNAs, including messenger RNA (mRNA), non-coding RNA (ncRNA), and different types of bases (A, C, G, U) (6–8). Highly dynamic RNA modifications play an important role in regulating RNA fate and are fundamental mechanisms for regulating the cellular transcriptome and proteome (9).

Many important modifications have been identified on mRNA and ncRNA, such as N6-methyladenosine (m⁶A) modification, N1-methyladenosine (m¹A) modification, 5-methylcytosine (m⁵C) modification, 7-methylguanosine (m⁷G) modification, etc. (Figure 1). Among them, the study about m⁶A modification is more in-depth, and a review of the literature shows that there are three main types of molecules involved in the modification: methyltransferases (i.e., writing proteins), demethylases (i.e., erasure proteins) and methyl-binding proteins (i.e., reading proteins), which perform catalysis, erasure and recognition, respectively. They act as a complex whole to dynamically regulate RNA localization, splicing, translation and degradation, which in turn affects RNA function and disease (10) (Figure 2).

In the next sections, we will briefly describe the regulatory mechanisms and functions of major RNA modifications in eukaryotic cells, such as m⁶A, m⁵C, m⁷G, and m¹A. We also highlight the biological and clinical roles of m⁶A modifications in renal diseases, such as AKI, CKD, diabetic kidney disease (DKD), lupus nephritis (LN), and renal cell carcinoma (RCC).

Methylation at the 5′ Cap is widely recognized as playing important roles in maintaining mRNA stability, precursor splicing, polyadenylation, transport, and translation initiation, and is a common modification found in the vast majority of eukaryotes. In addition, along with poly A binding protein, the changes at 3′ poly A have a role in outgoing nuclear transport, translation initiation, and mRNA structural stability maintenance (11). However only the head and tail of mRNA undergo these modifications, and the majority of these internal changes are m⁶A methylation changes. The term “m⁶A” refers to the dynamic and reversible methylation modification (N6-adenylation) that occurs on the 6th N of RNA adenylate and affects a variety of mRNA metabolic steps, including splicing, translation, nuclear export, and stability (Figure 2). m⁶A has the ability to influence gene expression and thus biological activities such as cell self-renewal, differentiation, invasion, and apoptosis (12).

The biological behavior of m⁶A is powerfully influenced by the concerted action of the write protein, the erase protein, and the read protein. These pivotal proteins collaboratively and intricately sculpt the epitranscriptome, playing a non-trivial role in shaping the phenotypic blueprint of cells, tissues, and organisms. For the m⁶A methyltransferase, which catalyzes the change from A to m⁶A on mRNA, Methyltransferase-like protein 3 (METTL3) and Methyltransferase-like protein 14 (METTL14) form a writing complex (13, 14) (Figure 2). m⁶A binding proteins that identify m⁶A methylation and start functional signaling include YTH m⁶A RNA binding protein 1–3 (YTHDF1-3), YTH domain containing 1–2 (YTHDC1-2), and insulin-like growth factor 2 mRNA-binding protein 1/2/3(IGF2BP1/2/3). Fat mass and obesity-associated protein (FTO) and alpha-ketoglutarate-dependent dioxygenase ALKB homolog 5 (ALKBH5), which are two protein demethylases, can remove m⁶A alterations from RNA, reversing and regulating the methylation-dependent process (15).

m⁶A, the most prevalent RNA modification, has been shown to exert its function in multiple ways, including splicing, export, decay, and translation initiation efficiency, to regulate mRNA fate. RNA modifications have been shown to be heavily involved in kidney development and the progression of disease. Additionally, it has been noted that m⁶A affects biological processes by upsetting stable base pairing, which controls a number of RNA functions. Most notably, it has been discovered that m⁶A is linked to a growing number of kidney disorders, including RCC, acute kidney injury, and chronic kidney disease. The RNA demethylase FTO is currently referred to be abundant in the kidney and governs the fibrotic process in obstructive nephropathy through the TGF-β signaling pathway, according to related studies (52). The degree of renal interstitial fibrosis was found to be strongly correlated with the m⁶A methylation alterations by Li et al. (53). We will next focus on the key role played by m⁶A in AKI, CKD, DN, LN, and RCC, as well as the related pathogenesis.

One of the chief reasons of acute kidney injury is IRI, a syndrome in which the injury increases instead after tissue ischemia restores blood flow. IRI can have negative effects in a clinical environment, such as decreased kidney graft survival and elevated client mortality (67–69). m⁶A mRNA changes have been observed in the heart, brain and kidney IRI in both in vivo and in vitro experiments (70–73). Inhibiting m⁶A methylation shields organs from the harm caused by IRI, which is assumed to be a major mechanism of m⁶A RNA alterations in organ damage.

As crucial subunit proteins of the m⁶A methylation transferase complex, METTL3 and METTL14 have recently been revealed to have a role in the emergence of IRI. In several studies, the upregulation of METTL3 was observed in IRI patients and IRI-induced AKI mouse models, indicating that IRI can lead to raised METTL3 and RNA m6A modification levels (74). A reduction in the production of Agt (angiotensinogen), Ren (renin), Ace (angiotensin I-converting enzyme), and At1r (angiotensin II, type I receptor-associated protein), together with the separation of Ren + cells from the capillary wall, lead to altered renal perfusion (75). Forkhead box D1 (Foxd1) also contributes to maintaining proper kidney development and regulating the shape of the renal capsule (75, 76). Through controlling Foxd1, METTL3 may contribute to renal IRI. Fodx1’s m⁶A level is negatively regulated and its mRNA expression level is elevated when METTL3 is suppressed, which affects renal perfusion (74) (Figure 4).

Via its proliferative and pro-fibrotic actions during recovery, Yes-associated protein 1 (YAP1) is engaged in renal regeneration and fibrosis following acute IRI (77). Contrarily, Xu et al. discovered that METTL14 knockout HK-2 cells and METTL14 knockout animals had lower levels of YAP1 mRNA methylation in their kidneys, which led to reduced YAP1 protein translocation, indicating that METTL14 can control IRI via suppressing YAP1 (78) (Figure 4). The fact that METTL14’s ex vivo renal IRI protection was destroyed by peptide 17’s suppression of the YAP1- transcriptional enhanced associate domain (TEAD) pathway suggests that RNA methylation is necessary for the activation of the YAP1 and YAP1-TEAD pathways and is required for METTL14’s function in renal IRI. This shows that renal IRI development involves m⁶A RNA methylation control.

Cisplatin and other platinum derivatives have been widely adopted as chemotherapeutic agents for their ability to exert anticancer effects by interfering with cell DNA and mitochondrial function. Despite their effectiveness in tumor therapy, these drugs are burdensome to renal function and often induce nephrotoxicity, leading to an important complication known as AKI (79). Recent research indicates that apoptosis, necrosis, and inflammation jointly represent hallmarks of CI-AKI (80).

Necrotic apoptosis is the principal cause of proximal tubular cell death in cisplatin-induced nephrotoxic AKI. When any major determinant of the mixed-spectrum kinase structural domain-like protein (MLKL), receptor interaction protein 1(RIP1), or necrotic pathway receptor interaction protein 3 (RIP3) is suppressed, cisplatin-induced proximal tubular damage in mice is reduced.

One research indicated that m⁶A methylation primarily functions in numerous pathways linked to metabolism, cell death, and oxidation, namely, there is a strong association between m⁶A methylation and CI-AKI regulation (81). This was identified through examining the discrepancies in m⁶A methylation and RNA expression in renal tissues between normal mice and CI-AKI animal models. Another study discovered that cisplatin caused the death of mice renal tubular epithelial cells, overexpression of METTL3 and METTL14 of m⁶A in cells, and a notable reduction in the expression of the methyl scavenger enzyme FTO, leading to a much higher level of RNA m⁶A modification and aggravating renal damage (82). FTO, on the other hand, may lessen the symptoms of CI-AKI by lowering the amounts of p53 mRNA and translation to lessen the apoptosis it causes.

One of sepsis’s most prevalent and serious consequences is SA-AKI (83). In one study, mmu-miR-7,212-5p-Hmox1 in iron death has been demonstrated as a significant RNA regulatory pathway implicated in the pathophysiological process of SA-AKI in a mouse model of septic AKI. The promotion of AKI development by m⁶A RNA methylation alteration in SA-AKI has been shown (84).

A growing number of studies in recent years have revealed that ncRNAs, particularly microRNAs (miRNAs), are connected to AKI (85). Endogenous ncRNAs called miRNAs have a variety of biological roles, including the ability to inhibit protein translation and control the negative feedback regulation of target mRNAs via complementary binding to the 3′-UTR of the target gene (86).

It has been discovered that m⁶A alterations play a role in the processing of pri-miRNAs or the splicing of pre-miRNAs, which regulate miRNA production. METTL3 increases the quantity of pri-miRNAs m⁶A and the expression of miRNAs. The demethyltransferase ALKBH5 prevents pri-miR-193a from being processed. To operate more effectively, miRNA controls the binding and location of METTL3 and FTO (87, 88)(Figure 4). In AKI, many miRNAs are implicated in controlling programmed cell death. According to Jia et al., miRNA-21 overexpression prevented cell death by decreasing PDCD4 while miRNA-21 silencing enhanced cell death in septic AKI (89).

DKD is a common microvascular complication of diabetes mellitus that leads to kidney disease. Prolonged hyperglycemia in diabetic patients induces the buildup of extracellular matrix in the glomerular and tubulointerstitial compartments, thickening and hyalinization of the intrarenal vascular system, and gradual decline of renal function (96, 97).

Numerous investigations have demonstrated the close connection between m⁶A and the onset of diabetes, but it is unclear how m⁶A contributes to the etiology of DKD. Ling Jiang et al. identified METTL3-mediated m⁶A modification as a vital cause of podocyte damage in DKD (98). When METTL3 was overexpressed, m⁶A modification in the kidney of type 1 and type 2 diabetic mice was dramatically elevated, and inflammation and apoptosis in high glucose (HG)-stimulated podocytes were significantly enhanced, and yet these reactions were decreased dramatically when it was shut down. The mechanism is that METTL3 induced pro-inflammatory and pro-apoptotic effects by modulating Notch signaling via the m⁶A alteration of tissue inhibitor of metalloproteinase 2 (TIMP2) in a way reliant on IGF2BP2.

Sirtuin-1 (SIRT1) deacetylase, which is abundantly found in renal tissues, has a role in kidney disorders by controlling a number of cellular biological processes, including apoptosis, autophagy, and inflammation, which helps to lessen acute kidney damage and treat kidney fibrosis (99, 100). In a separate investigation, mice with DKD had higher levels of m⁶A RNA and higher levels of METTL14 expression in their kidneys. When the expression of the METTL14 gene was reduced, SIRT1 mRNA m⁶A was prevented from being modified and degraded, autophagy was encouraged, apoptosis and an inflammatory response were reduced, and the wounded foot cells were thus safeguarded (101) (Figure 4).

In the kidneys of diabetes people and animals, the levels of histone deacetylase 5 (HDAC5), a member of the class II HDAC subfamily, are greater than average. In vitro cultures of human renal tubular cell lines (HK2) with high glucose levels revealed enhanced HDAC5 expression. According to studies on the etiology of DN, the TGF-β1 pathway has a significant pro-fibrotic role (102, 103). In diabetic tubular cells, hyperglycemia enhanced HDAC5 expression, and through elevation of TGF-β1, HDAC5 overexpression led to epithelial-mesenchymal transition in renal tubular cells. The epithelial-mesenchymal transition of renal tubular cells was impacted by the overexpression of METTL14, a vital component of the m⁶A methyltransferase complex, which also elevated m⁶A RNA methylation levels, boosted phosphatase and tensin homolog (PTEN) leading to PI3K/Akt pathway inactivation, decreased HDAC5 and TGF-β1 expression (104)(Figure 4).

α-klotho is an anti-aging gene that has been found to prevent tubular and glomerular injury and attenuate DKD in diabetic mice. METTL14 can also exacerbate high-glucose-induced glomerular endothelial cell injury and DKD by mediating the m⁶A modification of α-klotho and increasing its methylation level, leading to downregulation of α-klotho expression (105).

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by its heterogeneity and unknown etiology. Among its various manifestations, LN is the most frequent and severe, occurring in up to 60% of patients with SLE. LN can lead to significant kidney damage, with hematuria and proteinuria being common clinical features (106, 107).

m⁶A regulators in LN are connected to the immune microenvironment, according to some linked research, though the precise method by which m⁶A methylation is implicated in LN is unknown. Recent studies have revealed strong correlations between activated NK cells, immune responses, HLA genes, and m⁶A regulators in kidney tissues of patients with LN. Additionally, seven m⁶A markers [cell division cycle 5-like (CDC5L), cell division cycle 40(CDC40), heterogeneous nuclear ribonucleoprotein U (HNRNPU), nudix (nucleoside diphosphate linked moiety X)-type motif 21(NUDT21), poly(A) polymerase alpha(PAPOLA), polymerase (RNA) II (DNA directed) polypeptide B (POLR2B), and WW domain binding protein 4 (WBP4)] have been identified and implicated in the development and progression of LN. Among these markers, a positive correlation was observed between CDC40 and glomerular filtration rate (GFR), suggesting a potential protective effect (Figure 4). Conversely, CDC5L, HNRNPU, NUDT21, PAPOLA, POLR2B, and WBP4 were negatively correlated with GFR, raising the possibility that these genes may play a role in exacerbating renal damage in LN patients (108).

The expression of most m⁶A regulators in glomeruli differs significantly between healthy individuals and those with LN, indicating potential roles for these regulators in the pathogenesis of LN. Among these regulators, IGFBP3 plays an important role in maintaining a healthy immune system as a key m⁶A regulator, together with two key immune genes (CD14 and IDO1) (109).

It has been certified that urinary CD14 monocytes provide an effective biomarker for diagnosing LN (110). Meanwhile, IGFBP3, which controls somatic cell growth and proliferation, plays a critical role in healthy immune system maintenance, and supports the differentiation of naive CD8⁺ T cells. Additionally, free insulin-like growth factor-1 (IGF1) has been observed to have a convinced metabolic impact in patients with SLE. In MRL/LPR mice, the overexpression of IGF-1 and IGFBP2 in glomeruli has been associated with significant changes in renal morphology and function (111). Several studies have identified IGFBP2 as a promising biomarker for both SLE and LN. So IGFBP shows tremendous potential as a biomarker for autoimmune disorders (112).

Additionally, there is emerging evidence suggesting that ALKBH5 may serve as a key regulator in the pathogenesis of SLE (113). A potential link between reduced YTHDF2 expression and disease activity in SLE is also clarified (114).

Type I interferons (IFN-I) is a key player in the antiviral response of the innate immune system, and is also implicated in the pathogenesis of SLE. The methylation of RNA has been shown to play a crucial role in the production of IFN-I. For instance, m⁶A methylation of RNA mediated by METTL3 and FTO has been found to regulate the activation of TBK1-IRF3 pathway via heterogeneous nuclear ribonucleoprotein A2B1 (HNRNPA2B1), resulting in the promotion of IFN-I production (115) (Figure 4).

The above findings suggest that m6A methylation changes are important for the formation of LN. Hence, further analysis is necessary to elucidate the precise roles of m⁶A markers in the pathogenesis of LN and to develop more effective treatment strategies for this disease.

ADPKD is a monogenic disorder characterized by the development of numerous expanding tubular-derived cysts, which affects 85% of affected individuals leading to kidney failure (116). In a seminal study, Ramalingam et al. reported that METTL3 and its target RNA modification, m⁶A, play a crucial role in the pathogenesis of tubular cyst growth in ADPKD. METTL3 promotes cyst proliferation by increasing the methylation and translation of arginine-vasopressin receptor 2 (AVPR2) and c-Myc mRNA, which in turn enhance cyclic adenosine monophosphate and c-Myc signaling (Figure 4). Moreover, m⁶A content is also increased in kidney tissues of patients with ADPKD, suggesting the clinical relevance of METTL3/m⁶A signaling in ADPKD patients (117).

MN is characterized by the inflammation and thickening of the glomerular basement membrane, which primarily arises from autoimmunity and the deposition of immune complexes in the kidney. The phospholipase A2 receptor (PLA2R) has emerged as a prominent target antigen in MN (118). Similarly to IgAN, miRNAs have been implicated in the onset, progression, and potential prevention of MN, although the precise mechanisms remain elusive. Differential expression analysis of miRNAs and mRNAs has revealed the presence of regulatory network genes that may contribute to the development of membranous nephropathy through various signaling pathways, including mTOR, PDGFR-β, LKB1, and VEGF/VEGFR (119).

Unfortunately, the specific connection between m⁶A modification and membranous nephritis has yet to be established. m⁶A modification is known to play a role in regulating key pathophysiological processes in the kidneys, such as inflammation, fibrosis, and immune responses (Figure 4). These processes could potentially be implicated in the pathogenesis of membranous nephritis. Consequently, further investigations into the relationship between m⁶A modifications and MN are warranted, with a focus on potential alterations in m⁶A regulators, target genes, and their impact on disease onset and progression.

FSGS is a non-specific lesion primarily affecting podocytes rather than a distinct disease entity. Its main clinical manifestation is variable proteinuria, with or without accompanying nephrotic syndrome (120). Given the crucial role of podocytes in the progression of proteinuric nephropathy, investigating the impact of m⁶A modification on podocyte injury has gained significant attention.

To investigate the role of m⁶A in podocyte injury, Lu et al. performed a dual luciferase reporter gene assay in cultured human foot cells stimulated with Adriamycin or advanced glycosylation end products (AGE). They observed that METTL14 was significantly increased in renal biopsy samples from patients with FSGS and diabetic kidney disease, as well as in cultured human foot cells treated with Adriamycin or AGE in vitro.

Interestingly, knocking down METTL14 in podocytes not only exhibited notable improvements in glomerular function but also mitigated podocyte injury by activating autophagy while concurrently suppressing apoptosis and inflammation (101) (Figure 4).

This groundbreaking discovery and further investigations in this area hold the potential to uncover novel therapeutic strategies targeting m⁶A regulatory pathways specifically in podocytes.

IgAN is the most prevalent primary glomerular disease globally and one of the leading causes of chronic renal diseases. Studies have shown that approximately 40% of patients progress to end-stage renal diseases within 20 years of diagnosis. A distinguishing characteristic in the histological diagnosis of IgAN is the presence of explicit or implicit IgA staining in kidney biopsies (121).

Emerging data suggests that at least four key processes contribute to the development of IgAN: hereditary increase in galactose-deficient circulating IgA1, circulating antibodies directed against galactose-deficient IgA1, formation of pathogenic IgA1-containing immune complexes, mesangial deposition of IgA1-containing immune complexes, cell activation, and initiation of glomerular injury (122).

Notably, studies have identified elevated expression of JCHAIN in interstitial cells, suggesting its potential involvement in the accumulation of IgA1 and the initiation of in-situ deposits within the renal tissue (123).

IgAN also has shown associations with miRNAs, implicating their potential role in disease pathogenesis. Notably, miR-133a, miR-133b, and miR-185 have been observed to facilitate IgA1 deposition, while miR-17-5p appears to be linked to thylakoid proliferation and endocytosis transport, both contributing factors to the appearance of IgAN (124). In the realm of human cancers, IGF2BP2, an m⁶A reader, demonstrates interactions with diverse RNA species, including miRNAs, mRNAs, and lncRNAs, thereby affecting cancer development and progression (125). Though the precise relationship between m⁶A modification and the underlying mechanisms of IgAN remains unclear, leveraging existing research as a foundation paves the way for future comprehensive investigations aimed at unraveling the mechanism of this disease and identifying novel therapeutic targets.

An increasing number of kidney diseases, such as RCC, AKI and CKD, have been found to be associated with aberrant m⁶A. Today’s studies on the mechanisms of RNA methylation in renal diseases rely heavily on m⁶A, which has been found to affect normal physiological functions of the kidney by regulating the expression of target key genes (139, 140).

When m⁶A-related enzymes are abnormally expressed, they can interact with their downstream transcription factors to affect the mRNA synthesis process and promote or inhibit the development and progression of kidney disease. It was found that METTL3 overexpression of m⁶A in cells decreases Foxd1 content and causes apoptosis (74); METTL3 overexpression also leads to an increase in tgf-β-activated kinase 1 binding protein 3 (TAB3), resulting in inflammation and cell injury (10); METTL14 overexpression causes a decrease in YAP1, leading to reduced cell viability and thus acute kidney injury (71).

METTL3 is also present in chronic kidney disease. It positively regulates MALAT1 in TGF-β1-treated HK2 cells and affects the MALAT1/miR-145/FAK pathway in renal fibrosis, leading to renal fibrosis (102, 104). A significant decrease in the expression of the methyl scavenger enzyme FTO was accompanied by a significant increase in the level of RNA m⁶A modification and a concomitant increase in the amount of p53 mRNA, which in turn exacerbated renal damage (95).

METTL14 exacerbates high glucose-induced glomerular endothelial cell injury and DN by mediating m⁶A modification of α-klotho, increasing its methylation level and leading to downregulation of α-klotho expression (105). It can also affect the PTEN/PI3K/AKT pathway to increase HDAC5 and affect the epithelial-mesenchymal transition of renal tubular cells in DN (104). In contrast, METTL14 was significantly downregulated in RCC tissues (n = 580). Through the METTL14-YTHDF2-NEAT1_1 signaling axis, the growth and metastasis of RCC could be promoted (135).

The above-mentioned aberrantly expressed enzyme RNA methylation modification is a dynamic and reversible process. In renal diseases, reversing aberrant RNA methylation by targeting m⁶A regulators may delay the progression of renal disease. This suggests that targeting RNA m⁶A modification may be a novel strategy for the treatment of CKD and autophagy.

In recent years, researchers have made significant progress in developing targeted molecular inhibitors for m6A modifications. This approach is based on the observation that m⁶A regulators, such as METTL3, YTHDF1, and YTHDF2, are often dysregulated in tumor cells. These regulators are able to inhibit tumor cell proliferation, induce cancer cell death, and enhance immune response by increasing T cell transport and reducing immunosuppression (141).

Several inhibitors targeting FTO, such as rhodopsin, MO-I-500, and meclofenamic acid (MA), have been developed (142–144). Additionally, a highly potent and selective inhibitor of METTL3 and METTL14 called STM2457 has recently been identified. In preclinical models of acute myeloid leukemia, this inhibitor demonstrated significant anti-leukemic effects, suggesting that targeting m⁶A regulators holds promise for cancer therapy (145).

In addition to developing specific inhibitors of m6a regulatory factors, we may also want to start with epigenetic regulation, which plays a crucial role in gene expression and cellular function. The use of epigenetic inhibitors, such as DNA methyltransferase inhibitors or histone deacetylase inhibitors can modulate DNA methylation or histone modifications that may have an impact on kidney disease.

Given the complexity of kidney disease, we can first examine the enzymes that are aberrantly expressed by m6A modifications in patients, such as METTL3 and METTL14, which are expressed at elevated levels in patients with AKI (10, 78). Then, based on the results, we can make a diagnosis and administer a combination of treatments, such as using combinations of writing inhibitors, erasure modifiers, and reading protein modifiers, which may improve therapeutic efficacy.

While numerous potential therapeutic targets related to m6A methylation have been identified, there is a noticeable absence of clinical trials investigating the use of RNA methylation modifications in the treatment of renal diseases. Hence, there is a need for more targeted and meticulous clinical trials that utilize m6A methylation-associated enzymes for the treatment of renal diseases.

In summary, chemical modifications of RNA have an important role in many processes of cellular life and in the development of renal systemic diseases. In many renal diseases, RNA modifications, especially m⁶A, play an important role. For example, elevated or decreased levels of METTL3, a core component of m⁶A methyltransferase, can have a significant impact on the pathological manifestations of AKI, renal IRI, and DN. In contrast, high expression of METTL14 can have damaging effects on renal podocytes. In RCC, chemical modifications of RNA play a role in its developmental mechanism. The degree of expression of various methylation complexes showed abnormalities in cancer samples. These modifications can regulate the fate of multiple diseases. Therefore, chemical modifications of RNA have the potential to be used for targeted therapies (Table 1).

ZH [2nd author], YW, and LaY were involved in the conception of the study. LuY, ZH [14th author], HC, LC, and YL were involved in writing the article. ZH [2nd author] and YW made and modified figures. BW, YF, MZ, JL, FP, and YM critically revised the manuscript. All authors contributed to the article and approved the submitted version.